scholarly journals Selective In Vivo Visualization of Immune-Cell Infiltration in a Mouse Model of Autoimmune Myocarditis by Fluorine-19 Cardiac Magnetic Resonance

2013 ◽  
Vol 6 (2) ◽  
pp. 277-284 ◽  
Author(s):  
Ruud B. van Heeswijk ◽  
Jonathan De Blois ◽  
Gabriela Kania ◽  
Christine Gonzales ◽  
Przemyslaw Blyszczuk ◽  
...  
Keyword(s):  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Mouse Model ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Autoimmune Myocarditis

scholarly journals Indigo Pulverata Levis (Chung-Dae, Persicaria tinctoria) Alleviates Atopic Dermatitis-like Inflammatory Responses In Vivo and In Vitro

2022 ◽  
Vol 23 (1) ◽  
pp. 553
Author(s):  
Ga-Yul Min ◽  
Ji-Hye Kim ◽  
Tae-In Kim ◽  
Won-Kyung Cho ◽  
Ju-Hye Yang ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Hacat Cells ◽  
Serum Ige ◽  
Tnf Α ◽  
Inflammatory Chemokines

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with a type 2 T helper cell (Th2) immune response. The IndigoPulverata Levis extract (CHD) is used in traditional Southeast Asian medicine; however, its beneficial effects on AD remain uninvestigated. Therefore, we investigated the therapeutic effects of CHD in 2,4-dinitrochlorobenzene (DNCB)-induced BALB/c mice and tumor necrosis factor (TNF)-α- and interferon gamma (IFN)-γ-stimulated HaCaT cells. We evaluated immune cell infiltration, skin thickness, and the serum IgE and TNF-α levels in DNCB-induced AD mice. Moreover, we measured the expression levels of pro-inflammatory cytokines, mitogen-activated protein kinase (MAPK), and the nuclear factor-kappa B (NF-κB) in the mice dorsal skin. We also studied the effect of CHD on the translocation of NF-κB p65 and inflammatory chemokines in HaCaT cells. Our in vivo results revealed that CHD reduced the dermis and epidermis thicknesses and inhibited immune cell infiltration. Furthermore, it suppressed the proinflammatory cytokine expression and MAPK and NF-κB phosphorylations in the skin tissue and decreased serum IgE and TNF-α levels. In vitro results indicated that CHD downregulated inflammatory chemokines and blocked NF-κB p65 translocation. Thus, we deduced that CHD is a potential drug candidate for AD treatment.

Effects of ASCL1 expression on tumorigenesis and immune cell infiltration in a syngenic mouse model of lung adenocarcinoma

2019 ◽  
Author(s):  
Naoya Miyashita ◽  
Masafumi Horie ◽  
Yu Mikami ◽  
Hirokazu Urushiyama ◽  
Kensuke Fukuda ◽  
...  
Keyword(s):  
Mouse Model ◽  
Lung Adenocarcinoma ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

scholarly journals N-Acetyl-Seryl-Aspartyl-Lysyl-Proline: mechanisms of renal protection in mouse model of systemic lupus erythematosus

2015 ◽  
Vol 308 (10) ◽  
pp. F1146-F1154 ◽  
Author(s):  
Tang-Dong Liao ◽  
Pablo Nakagawa ◽  
Branislava Janic ◽  
Martin D'Ambrosio ◽  
Morel E. Worou ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Immune Cell ◽  
Organ Damage ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Renal Protection ◽  
Systemic Lupus ◽  
Autoimmune Myocarditis

Systemic lupus erythematosus is an autoimmune disease characterized by the development of auto antibodies against a variety of self-antigens and deposition of immune complexes that lead to inflammation, fibrosis, and end-organ damage. Up to 60% of lupus patients develop nephritis and renal dysfunction leading to kidney failure. N-acetyl-seryl-aspartyl-lysyl-proline, i.e., Ac-SDKP, is a natural tetrapeptide that in hypertension prevents inflammation and fibrosis in heart, kidney, and vasculature. In experimental autoimmune myocarditis, Ac-SDKP prevents cardiac dysfunction by decreasing innate and adaptive immunity. It has also been reported that Ac-SDKP ameliorates lupus nephritis in mice. We hypothesize that Ac-SDKP prevents lupus nephritis in mice by decreasing complement C5-9, proinflammatory cytokines, and immune cell infiltration. Lupus mice treated with Ac-SDKP for 20 wk had significantly lower renal levels of macrophage and T cell infiltration and proinflammatory chemokine/cytokines. In addition, our data demonstrate for the first time that in lupus mouse Ac-SDKP prevented the increase in complement C5-9, RANTES, MCP-5, and ICAM-1 kidney expression and it prevented the decline of glomerular filtration rate. Ac-SDKP-treated lupus mice had a significant improvement in renal function and lower levels of glomerular damage. Ac-SDKP had no effect on the production of autoantibodies. The protective Ac-SDKP effect is most likely achieved by targeting the expression of proinflammatory chemokines/cytokines, ICAM-1, and immune cell infiltration in the kidney, either directly or via C5-9 proinflammatory arm of complement system.

scholarly journals Impact of Reduced ATGL-Mediated Adipocyte Lipolysis on Obesity-Associated Insulin Resistance and Inflammation in Male Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (10) ◽  
pp. 3610-3624 ◽  
Author(s):  
Gabriele Schoiswohl ◽  
Maja Stefanovic-Racic ◽  
Marie N. Menke ◽  
Rachel C. Wills ◽  
Beth A. Surlow ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Target Genes ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Peroxisome Proliferator ◽  
Immune Cell Infiltration ◽  
Lipid Uptake ◽  
Peroxisome Proliferator Activated Receptor ◽  
Triacylglycerol Hydrolysis

Emerging evidence suggests that impaired regulation of adipocyte lipolysis contributes to the proinflammatory immune cell infiltration of metabolic tissues in obesity, a process that is proposed to contribute to the development and exacerbation of insulin resistance. To test this hypothesis in vivo, we generated mice with adipocyte-specific deletion of adipose triglyceride lipase (ATGL), the rate-limiting enzyme catalyzing triacylglycerol hydrolysis. In contrast to previous models, adiponectin-driven Cre expression was used for targeted ATGL deletion. The resulting adipocyte-specific ATGL knockout (AAKO) mice were then characterized for metabolic and immune phenotypes. Lean and diet-induced obese AAKO mice had reduced adipocyte lipolysis, serum lipids, systemic lipid oxidation, and expression of peroxisome proliferator-activated receptor alpha target genes in adipose tissue (AT) and liver. These changes did not increase overall body weight or fat mass in AAKO mice by 24 weeks of age, in part due to reduced expression of genes involved in lipid uptake, synthesis, and adipogenesis. Systemic glucose and insulin tolerance were improved in AAKO mice, primarily due to enhanced hepatic insulin signaling, which was accompanied by marked reduction in diet-induced hepatic steatosis as well as hepatic immune cell infiltration and activation. In contrast, although adipocyte ATGL deletion reduced AT immune cell infiltration in response to an acute lipolytic stimulus, it was not sufficient to ameliorate, and may even exacerbate, chronic inflammatory changes that occur in AT in response to diet-induced obesity.

Tumor-derived GDF-15 to suppress t-lymphocyte recruitment to the tumor microenvironment resulting in resistance to ANTI-PD-1 treatment.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14532-e14532
Author(s):  
Joerg Wischhusen ◽  
Markus Haake ◽  
Neha Vashist ◽  
Sabrina Genßler ◽  
Kilian Wistuba-Hamprecht ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Cell ◽  
Serum Levels ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
T Cell Infiltration ◽  
Melanoma Patients

e14532 Background: Growth and differentiation factor 15 (GDF-15) is a divergent member of the TGF-β superfamily with low to absent expression in healthy tissue. GDF-15 has been linked to feto-maternal immune tolerance, to prevention of excessive immune cell infiltration during tissue damage, and to anorexia. Various major tumor types secrete high levels of GDF-15. In cancer patients, elevated GDF-15 serum levels correlate with poor prognosis and reduced overall survival (OS). Methods: Impact of a proprietary GDF-15 neutralizing antibody (CTL-002) regarding T cell trafficking was analyzed by whole blood adhesion assays, a HV18-MK melanoma-bearing humanized mouse model and a GDF-15-transgenic MC38 model. Additionally, patient GDF-15 serum levels were correlated with clinical response and overall survival in oropharyngeal squamous cell carcinoma (OPSCC) and melanoma brain metastases. Results: In whole blood cell adhesion assays GDF-15 impairs adhesion of T and NK cells to activated endothelial cells. Neutralization of GDF-15 by CTL-002 rescued T cell adhesion. In HV18-MK-bearing humanized mice CTL-002 induced a strong increase in TIL numbers. Subset analysis revealed an overproportional enrichment of T cells, in particular CD8+ T cells. As immune cell exclusion is detrimental for checkpoint inhibitor (CPI) therapy, a GDF-15-transgenic MC38 model was tested for anti-PD-1 therapy efficacy. In GDF-15 overexpressing MC38 tumors response to anti PD-1 therapy was reduced by 90% compared to wtMC38 tumors. Combining aPD-1 with CTL-002 resulted in 50% of the mice rejecting their GDF-15 overexpressing tumors. Clinically, inverse correlations of GDF-15 levels with CD8+ T cell infiltration were shown for HPV+ OPSCC and for melanoma brain metastases. GDF-15 serum levels were significantly higher in HPV- than in HPV+ OPSCC patient (p < 0.0001). Low GDF-15 levels corresponded to longer OS in both HPV- and HPV+ OPSCC. In two independent melanoma patient cohorts treated with nivolumab or pembrolizumab low baseline serum GDF-15 levels were predictive for clinical response to anti-PD1 treatment and superior OS. Bivariate analysis including LDH indicates that GDF-15 independently predicts poor survival in aPD-1 treated melanoma patients. Conclusions: Taken together our in vitro and in vivo data show that elevated GDF-15 levels block T-cell infiltration into tumor tissues. Neutralizing GDF-15 with CTL-002 restores the ability of T cells to extravasate blood vessels and enter tumor tissue both in vitro and in vivo. In melanoma, patients with higher GDF-15 levels have significantly shorter survival and are less likely to respond to anti-PD1 therapy. GDF-15 may thus serve as a new predictive biomarker for anti-PD1 response, but most importantly also represents a novel target for cancer immunotherapy to improve tumor immune cell infiltration and response to anti-PD1 therapy.

scholarly journals Δ9-Tetrahydrocannabinolic Acid markedly alleviates liver fibrosis and inflammation in murine models of chemically- and obesity-induced liver injury

2020 ◽  
Author(s):  
Beatriz Carmona-Hidalgo ◽  
Isabel González-Mariscal ◽  
Adela García-Martín ◽  
Francisco Ruiz-Pino ◽  
Giovanni Appendino ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Fatty Liver ◽  
Immune Cell ◽  
Cannabis Sativa ◽  
Cell Infiltration ◽  
Western World ◽  
Immune Cell Infiltration ◽  
Alcoholic Fatty Liver

ABSTRACTBackgroundNon-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, and it is closely associated to obesity, type 2 diabetes mellitus, and dyslipidemia. Hepatocellular stellate cells (HSCs) activation by oxidative stress and inflammation is the hallmark of liver fibrosis and leads to cirrhosis and liver failure resistant to pharmacological management. Cannabinoids have been suggested as a potential therapy for liver fibrosis, prompting us to explore the antifibrotic and anti-inflammatory effects of Δ9-THCA-A, a major non-psychotropic cannabinoid from Cannabis sativa L., in animal models of NAFLD.MethodsNon-alcoholic liver fibrosis was induced in mice by CCl4 treatment or, alternatively, by 23-week high fat diet (HFD) feeding. Δ9-THCA was administered daily intraperitoneally during the CCl4 treatment or during the last 3 weeks in HFD-fed mice. Liver fibrosis and inflammation were assessed by immunochemistry and qPCR. Blood glucose and plasma insulin, leptin and triglyceride levels were measured in HFD mice.ResultsΔ9-THCA significantly attenuated CCl4-induced liver fibrosis and inflammation and reduced T cell and macrophage infiltration. Mice fed HFD for 23 weeks developed severe obesity (DIO), fatty liver and marked liver fibrosis, accompanied by immune cell infiltration. Δ9-THCA, significantly reduced body weight and adiposity, improved glucose tolerance, and drastically attenuated DIO-induced liver fibrosis and immune cell infiltration.ConclusionsΔ9-THCA prevents liver fibrogenesis in vivo, providing a rationale for additional studies on the medicinal use of this cannabinoid, as well as cannabis preparations containing it, in the treatment of liver fibrosis and the management of NAFLD.

Construction of Hyaluronic Acid-CeO2 Conjugated Composite Nanoparticles and Their Activity Efficiency in Diabetic Retinopathy Alleviation

2021 ◽  
Vol 17 (11) ◽  
pp. 2219-2225
Author(s):  
Jingzhi Shao ◽  
Jingjing Wan ◽  
Fengyan Zhang ◽  
Lirong Zhang
Keyword(s):  
Diabetic Retinopathy ◽  
Hyaluronic Acid ◽  
Mouse Model ◽  
Clinical Efficacy ◽  
Structural Integrity ◽  
Foreign Body Reaction ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Retinal Structure

We developed an effective nanoparticle-biomaterial in alleviating diabetic retinopathy (DR), hyaluronic acid (HA)-CeO2, composed mainly of CeO2 and HA. To demonstrate its anti-DR capacity, retinal cells from a B6/J mouse model were used to compare the efficiency of PEI-CeO2 and HA-CeO2. We investigated the transport performance, histolysis, immune cell infiltration, angiogenesis, and hyperemia induced by the transport system. The structural integrity, microvascular apoptosis, and superoxide and peroxide concentrations in the retina were measured to evaluate the clinical efficacy of CeO2. The infiltration efficiency of HA-CeO2 was higher than that of PEI-CeO2. Lower levels of foreign body reaction were evident for HA-CeO2 with less histolysis, immune cell infiltration, angiogenesis, and hyperemia. The clinical efficacy of HA-CeO2 in terms of preservation of retinal structure and lowering of microvascular apoptosis and superoxide and peroxide concentrations was superior to those of PEI-CP. HA-CeO2 was shown to have significant antioxidation and anti-vascular injury capacity in a mouse model, and may be a potential compound nanodrug for DR treatment in the future.

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